Perspectives in PDK1 evolution

Abstract

Protein kinases belonging to the AGC group modulate many diverse cellular processes in all eukaryotes. One important way to regulate AGC kinases is through phosphorylation by the upstream kinase PDK1. PDK1 localization and activity usually depend on interactions with phospholipids, which are mediated by a conserved lipid-binding pleckstrin homology (PH) domain. We recently analyzed putative PDK1 sequences from 17 photosynthetic organisms, finding that PDK1s from vascular and nonvascular species seem to be distinguished by the presence or absence of a PH domain, respectively. The only other reported PDK1 lacking a PH domain is from yeast (Saccharomyces cerevisiae). These observations raise questions about how plant PDK1s and their lipid-binding capabilities have evolved in relation to other eukaryotes, and what this means for PDK1 function. Here we use 100 PDK1 sequences from diverse organisms to discuss possible evolutionary aspects of plant PDK1 structure and lipid binding.

The reduced kinome of Ostreococcus tauri: core eukaryotic signalling components in a tractable model species

“…Phylogeny across diverse eukaryotes has revealed a complex patchwork of conservation that suggests a history of successive contractions and expansions in the AGC kinases [62]. One of the few constants across eukaryote lineages is the Phosphoinositide-Dependent Kinase-1 (PDK1).…”

“…Members of the AGC family are cytoplasmic S/T kinases (named after PKA, PKG, and PKC), some of which contain Ca 2+ sensing domains, regulate glycogen metabolism and ion channel conductance. Phylogeny across diverse eukaryotes has revealed a complex patchwork of conservation that suggests a history of successive contractions and expansions in the AGC kinases [ 62 ]. One of the few constants across eukaryote lineages is the Phosphoinositide-Dependent Kinase-1 (PDK1).…”

“…Existing work has revealed an expansion of S6K and NDR into large and ubiquitous families across the kinomes of higher plants [ 40 ]. PDK1 is present throughout the green lineage but many orthologs, including O. tauri , lack a functional lipid-binding domain [ 62 ]. PKA- and PKG-like kinases exist in higher plants and other Streptophytes [ 40 ] but these have diverged substantially: orthologs from the Chlorophyta such as O. tauri have closer sequence similarity to metazoan and fungal sequences than the closest sequences in Streptophytes have to any of these groups.…”

“…PDK1 is the most important member of the AGC family in terms of phylogeny as it represents a highly conserved kinase, which has changed little since the divergence of eukaryotic AGCs [ 62 ]. PDK1 in O. tauri is most similar to the two A. thaliana orthologs (1.26).…”

“…It also groups closer to H. sapiens (1.67) than S. cerevisiae orthologs (1.81) (Figure 4 A). PDK1 is thought to be a basal conserved kinase, which predates the divergence of ePKs [ 62 ], and is therefore used to root AGC phylogenies (Figure 4 C and D). PDK1 has also been termed the ‘master kinase’ of AGC signal transduction [ 64 ] because of its critical role in cellular survival through the activation of Protein Kinase B (PKB, also known as Akt) and S6K in humans [ 65 ].…”